Studying Glioblastoma in a Human Organoid Tumor Transplantation Model
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PROVIDER: PRJNA1226668 | ENA |
REPOSITORIES: ENA
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Project description:Studying Glioblastoma in a Human Organoid Tumor Transplantation Model
| PRJNA1226667 | ENA
Project description:Intestinal epithelial damage predisposes to chronic disorders like inflammatory bowel disease. The organoid model allows the cultivation, expansion and analysis of primary intestinal epithelial cells and has been instrumental in studying epithelial behavior in homeostasis and disease. Recent advances in organoid transplantation lay the base for studies of human epithelial cell behavior within the intestinal tissue context. It remained unclear how organoid transplantation into the colon affects epithelial phenotypes, which is key to assessing the model’s suitability to study human epithelial cells. We employed Deep Visual Proteomics, integrating AI-guided cell classification, laser microdissection, and an improved proteomics pipeline to study the human colon mucosa. Thereby, we created the first cell type-resolved proteomics dataset of human intestinal epithelial cells within human tissue, in vitro organoids, and the murine colon post-xenotransplantation. Our findings reveal that in vitro conditions induce a proliferative organoid phenotype, which is reversible upon transplantation and adjustment of organoid culturing conditions.
2025-09-11 | PXD052341 | Pride
Project description: Not available
| S-EPMC12262450 | biostudies-literature
Project description:Glioblastoma shows marked spatial heterogeneity and hypoxia-associated signaling. Here, we performed probe-based Xenium single-cell spatial transcriptomics on a primary human glioblastoma sample and on a patient-derived glioblastoma organoid cultured on a brain slice. The aim was to assess the in situ single-cell expression of hypoxia-related genes, with a particular focus on VEGFA and CXCL12. These datasets provide spatially resolved transcriptomic information to study hypoxic niches and tumor microenvironmental interactions in glioblastoma.
2026-03-17 | GSE324268 | GEO
Project description:An organoid-based transplantation model reveals genetic interactions potentiating niche-independent gastric carcinogenesis
| PRJNA792333 | ENA
Project description:Background: Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterise extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems.Methods: Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterisation was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analysed by high-resolution mass spectrometry.Results: We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR- 323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response.Conclusion: Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.
2024-04-09 | PXD047328 | Pride
Project description:It is currently challenging to adequately model the growth and migration of glioblastoma using 2D in vitro culture systems as they quickly lose the original, patient-specific identity and heterogeneity. However, with the advent of 3D cell cultures and human induced pluripotent stem cells (iPSCs)-derived cerebral organoids (COs), studies demonstrate that the glioblastoma-cerebral organoid (GLICO) co-culture model helps to preserve the phenotype of the patient-specific tissue. Here we aimed to set up such a model using mature COs and develop a pipeline for subsequent analysis of co-cultured glioblastoma. Our data demonstrates that the growth and migration of the glioblastoma cell line within the mature COs are significantly increased in the presence of extracellular matrix proteins, shortening the time needed for glioblastoma to initiate migration. We also describe in detail the method for the visualization and quantification of these migrating cells within the GLICO model. Lastly, we show that this co-culture model (and the human brain-like microenvironment) can significantly transform the gene expression profile of the established U87 glioblastoma cell line into proneural and classical glioblastoma cell types.
2023-02-22 | GSE216626 | GEO
Project description:Patient derived organoids (PDOs) have been established as a 3D culture model which closely recapitulates the in vivo tumor biology. However, one limitation of this culture model is the lack of tumor microenvironment which has a significant role in tumor progression and drug response. To address this, we established and molecularly characterized a novel 3D co-culture model of colorectal cancer (CRC) based on PDOs and patient matched fibroblasts. Both normal and cancer associated fibroblasts, NFs and CAFs respectively, were able to support organoid growth without addition of niche factors to the media. Additionally, co-cultures showed closer resemblance to primary patient material than organoid mono-cultures as evaluated by histology. Finally, RNA gene expression signatures of tumor cells and fibroblasts isolated from mono- or co-cultures demonstrated that co-cultures support greater cell type heterogeneity. In this proteomics dataset we compared pairs of NFs and CAFs derived from five patients. Collectively, we present a newly established human derived organoid-fibroblast model which, closely recapitulates in vivo tumor heterogeneity and involves the tumor microenvironment.
2023-03-14 | PXD032047 | Pride
Project description:Human iPSC-derived kidney organoids have the potential to revolutionize discovery, but assessing their consistency and reproducibility across iPSC lines, and reducing the generation of off-target cells remain an open challenge. Here, we used single cell RNA-Seq (scRNA-Seq) to profile 450,118 cells to show that organoid composition and development are comparable to human fetal and adult kidneys. Although cell classes were largely reproducible across iPSC lines, time points, protocols, and replicates, cell proportions were variable between different iPSC lines. Off-target cell proportions were the most variable. Prolonged in vitro culture did not alter cell types, but organoid transplantation under the mouse kidney capsule diminished off-target cells. Our work shows how scRNA-seq can help score organoids for reproducibility, faithfulness and quality, that kidney organoids derived from different iPSC lines are comparable surrogates for human kidney, and that transplantation enhances their formation by diminishing off-target cells.
2019-11-04 | GSE136314 | GEO